This research project is designed to investigate the replication of enveloped RNA viruses in mouse peritoneal macrophages. The major emphasis will be placed on studies with lactic dehydrogenase virus (LDV) - a virus that causes a persistent, non-cytopathic infection in mice, appears to replicate only in macrophages, and causes diverse effects on the animal's immune system. We have been able to grow LDV in somatic cell hybrids between mouse macrophages and SV-40 transformed human fibroblasts and are now able to study persistent infection by this virus in cultured cells. Our specific objectives are: (1) to identify the steps in LDV replication in permissive cells and then determine which of these are prevented in non-permissive hosts; (2) to examine persistent infection by LDV and, in particular, characterize defective-interfering particles which may accumulate; and (3) to initiate studies on viral replication in mice genetically-altered in the immune response. These strains, BSVS and BRVR, differ in their susceptibility to arbo B (flavi) viruses. Sensitivity or resistance may reside in macrophages and may be related to the generation of defective-interfering particles. We shall examine these mice, and cells obtained from them, for differences in their response to LDV.